title: Using computational techniques in fragment-based drug discovery.
abstract: Fragment-based drug discovery has emerged over the past 15 years as an effective lead discovery paradigm that is complementary to traditional high-throughput screening. The starting point for fragment-based drug discovery is the identification of low-molecular weight, typically low-affinity compounds that bind to a target of interest. These fragments can then be elaborated by growing or linking to create compounds with high affinity and selectivity. A wide variety of techniques from the computational chemistry tool chest can be applied in a fragment-based project. The computational tools are equally useful in combination with experimental-binding determination or in a completely in silico design procedure. This chapter will outline these techniques, their utility, and their validation in the design of novel lead compounds.
authors.affiliation: Structural Biology, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Spring House, Pennsylvania, USA.
authors.forename: Renee L
authors.initials: RL
authors.lastname: Desjarlais
mesh_terms: D019295:Computational Biology; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008958:Models, Molecular; D011485:Protein Binding; D054852:Small Molecule Libraries
chemical_list: D054852:Small Molecule Libraries